title: Up-regulation of SOX9 in sertoli cells from testiculopathic patients accounts for increasing anti-mullerian hormone expression via impaired androgen receptor signaling.
abstract: BACKGROUND
  Testosterone provokes Sertoli cell maturation and represses AMH production. In adult patients with Sertoli-cells-only syndrome (SCOS) and androgen insensitivity syndrome (AIS), high level of AMH expression is detected in Sertoli cells due to defect of androgen/AR signaling.
  
  
  OBJECTIVE
  We postulated that up-regulation of SOX9 due to impairment of androgen/AR signaling in Sertoli cells might explain why high level of anti-Mullerian hormone (AMH) expression occur in these testiculopathic patients.
  
  
  METHODS
  Biological research of testicular specimens from men with azoospermia or mouse. The serum hormone levels were studied in 23 men with obstructive azoospermia, 33 men with SCOS azoospermia and 21 volunteers with normal seminograms during a period of 4 years. Immunohistochemical staining and reverse-transcription PCR were used to examine the relationships among AR, SOX9 and AMH expression in adult human and mouse testes. The ability of AR to repress the expression of SOX9 and AMH was evaluated in vitro in TM4 Sertoli cells and C3H10T1/2 cells.
  
  
  RESULTS
  SCOS specimens showed up-regulation of SOX9 and AMH proteins but down-regulation of AR proteins in Sertoli cells. The mRNA levels of AR were significantly lower and the SOX9, AMH mRNA levels higher in all SCOS patients compared to controls (P< 0.05). The testosterone levels in the SCOS patients were within the normal range, but most were below the median of the controls. Furthermore, our in vitro cell line experiments demonstrated that androgen/AR signaling suppressed the gene and protein levels of AMH via repression of SOX9.
  
  
  CONCLUSIONS
  Our data show that the functional androgen/AR signaling to repress SOX9 and AMH expression is essential for Sertoli cell maturation. Impairment of androgen/AR signaling promotes SOX9-mediated AMH production, accounts for impairments of Sertoli cells in SCOS azoospermic patients.
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan ; Graduate Institute of Clinical Medical Sciences, Chang Gung University, Kaohsiung, Taiwan ; Hormone Research Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Kuo-Chung
authors.initials: KC
authors.lastname: Lan
authors.forename: Yen-Ta
authors.initials: YT
authors.lastname: Chen
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
authors.forename: Yung-Chiao
authors.initials: YC
authors.lastname: Chang
authors.forename: Hsin-Jung
authors.initials: HJ
authors.lastname: Lin
authors.forename: Ko-En
authors.initials: KE
authors.lastname: Huang
authors.forename: Hong-Yo
authors.initials: HY
authors.lastname: Kang
mesh_terms: D013734:Androgen-Insensitivity Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D054304:Anti-Mullerian Hormone / Q000235:genetics / Q000378:metabolism*; D053713:Azoospermia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D011944:Receptors, Androgen / Q000378:metabolism*; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D054331:Sertoli Cell-Only Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012708:Sertoli Cells / Q000378:metabolism*; D015398:Signal Transduction; D013737:Testis / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
chemical_list: D011944:Receptors, Androgen; D055758:SOX9 Transcription Factor; D054304:Anti-Mullerian Hormone